Highlights
- High-resolution map of human NK cells shows tissue-driven distribution across ages
- Differentiated NK cells predominate in blood, bone marrow, spleen, and lungs
- Tissue-resident NK cells exhibit specific adaptations in mucosal and lymphoid sites
- Lymph nodes and intestines are reservoirs for precursor and immature NK cells
Summary
Immune responses in diverse tissue sites are critical for protective immunity and homeostasis. Here, we investigate how tissue localization regulates the development and function of human natural killer (NK) cells, innate lymphocytes important for anti-viral and tumor immunity. Integrating high-dimensional analysis of NK cells from blood, lymphoid organs, and mucosal tissue sites from 60 individuals, we identify tissue-specific patterns of NK cell subset distribution, maturation, and function maintained across age and between individuals. Mature and terminally differentiated NK cells with enhanced effector function predominate in blood, bone marrow, spleen, and lungs and exhibit shared transcriptional programs across sites. By contrast, precursor and immature NK cells with reduced effector capacity populate lymph nodes and intestines and exhibit tissue-resident signatures and site-specific adaptations. Together, our results reveal anatomic control of NK cell development and maintenance as tissue-resident populations, whereas mature, terminally differentiated subsets mediate immunosurveillance through diverse peripheral sites.
Highlights
- 人体NK细胞的高分辨率图谱显示在不同年龄段与组织类型相关的分布特征
- 血液、骨髓、脾脏、肺等器官中主要的NK细胞类型不同
- 在粘膜和淋巴位点组织原位的NK细胞显示出特异的适应性
- 淋巴结和肠是祖先细胞和未成熟NK细胞的储藏位置
Summary
不同组织的免疫响应对于保护性免疫和免疫平衡至关重要。在这篇文章里，我们研究了组织定位如何调节人体NK细胞的发生发展及功能，NK细胞是一种固有的淋巴细胞，对于抗病毒，抗肿瘤免疫非常重要。通过整合取自60个供体的血液、淋巴器官、粘膜组织等位点的NK细胞，对其进行多维分析，我们鉴定出了NK细胞亚群分布、成熟、功能存在组织特异的模式，这些模式可以在不同年龄段和个体之间维持。成熟和终端分化的NK细胞，功能更强，主要存在于血液、骨髓、脾脏和肺中，并且在转录水平有相似的模式。相比之下，祖先细胞和未成熟的NK细胞，功能没那么强，主要集中在淋巴结和肠组织，并且显示出组织特异的特征和适应性。总的来说，我们的结果揭示了不同组织的NK细胞的发生发展、维持，而成熟的终端分化的NK细胞亚群借助不同的外周位点调节免疫监视。
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